Association of high-risk CT coronary artery plaque features with major adverse cardiovascular events: a prespecified secondary analysis of the DISCHARGE trial

: Szilveszter, Bálint; Biavati, Federico; Sørum, Charlotte; Benedek, Theodora; Donnelly, Patrick; Rodriguez-Palomares, José F.; Erglis, Andrejs; Štěchovský, Cyril; Šakalytė, Gintarė; Ađić, Nada Čemerlić; Gutberlet, Matthias; Dodd, Jonathan D.; Diez, Ignacio; Davis, Gershan; Zimmermann, Elke; Kepka, Cezary; Vidakovic, Radosav; Francone, Marco; Ilnicka-Suckiel, Małgorzata; Plank, Fabian; Knuuti, Juhani; Faria, Rita; Schröder, Stephen; Berry, Colin; Saba, Luca; Ruzsics, Balazs; Rieckmann, Nina; Kubiak, Christine; Schultz Hansen, Kristian; Müller-Nordhorn, Jacqueline; Maurovich-Horvat, Pal; Vall-Lamora, Helena Domínguez; Benedek, Imre; Orr, Clare; Valente, Filipa; Zvaigzne, Ligita; Suchánek, Vojtěch; Jankauskas, Antanas; Ađić, Filip; Woinke, Michael; Mulvihill, Niall; Lecumberri, Iñigo; Thwaite, Erica; Kruk, Mariusz; Neskovic, Aleksandar N.; Mancone, Massimo; Kuśmierz, Donata; Feuchtner, Gudrun Maria; Pietilä, Mikko; Ribeiro, Vasco Gama; Drosch, Tanja; Delles, Christian; Boi, Alberto; Fisher, Michael; Merkely, Béla; Hansen, Thomas Fritz; Aurelian, Rosca; Kelly, Stephanie; García del Blanco, Bruno; Rubio, Ainhoa; Boussoussou, Melinda; Jørgensen, Tem; Rodean, Ioana; Regan, Susan; Calabria, Hug Cuéllar; Vattay, Borbála; Hodas, Roxana; Napp, Adriane Elisabeth; Haase, Robert; Feger, Sarah; Mohamed, Mahmoud M. A.; Serna-Higuita, Lina M.; Neumann, Konrad; Dreger, Henryk; Rief, Matthias; Wieske, Viktoria; Williams, Michelle C.; Estrella, Melanie; Bosserdt, Maria; Martus, Peter; Kofoed, Klaus F.; Dewey, Marc

Publisher: Springer Nature

: 2026

European Radiology

: 0938-7994

: 1432-1084

DOI: https://doi.org/10.1007/s00330-025-12146-3

: https://doi.org/10.1007/s00330-025-12146-3

: https://research.utu.fi/converis/portal/detail/Publication/515660785

Objectives

The prognostic role of high-risk plaque (HRP) features, including high coronary calcium scores detected by CT, beyond traditional cardiovascular risk factors and obstructive coronary artery disease (CAD), remains uncertain. This study evaluated the prognostic value of a combined HRP definition in stable chest pain patients with low-to-intermediate pretest probability of CAD.

Materials and methods

This prespecified analysis included participants randomized to the CT arm of the pragmatic, prospective 26-center European DISCHARGE trial (NCT02400229). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke); the secondary endpoint was expanded MACE (transient ischemic attack and major procedure-related complications). Our combined HRP definition was any coronary plaque with positive remodeling, napkin-ring sign, low attenuation, or total calcium score ≥ 400 Agatston units.

Results

Among 1745 participants (age: 60 ± 10 years, 990 female), 35 MACE and 47 expanded MACE occurred at a median follow-up of 3.5 years (IQR: 2.9–4.2). After risk factor adjustment, the combined HRP definition was associated with a higher risk of MACE (HR: 3.81; 95% CI: 1.01–14.6; p = 0.050) and remained significantly associated with expanded MACE (HR: 0.21; 95% CI: 1.07–9.66; p = 0.038). Patients with both HRP and obstructive CAD conferred the highest MACE (HR: 8.78; 95% CI: 2.90–26.6; p < 0.001) and expanded MACE risk (HR: 7.31; 95% CI: 3.06–17.48; p < 0.001) compared with patients without HRP or obstructive CAD. HRP alone showed a prognostic impact comparable to obstructive CAD alone.

Conclusion

HRP features on coronary CT provide incremental predictive value for MACE, comparable to obstructive CAD, after adjusting for traditional cardiovascular risk factors in this large pan-European cohort.

s00330-025-12146-3.pdf

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This study was funded by grants from the EU-FP7 Framework Program (FP 2007-2013, EC-GA 603266) to M.D. and others: Berlin Institute of Health (grant from Digital Health Accelerator); British Heart Foundation (Centre of Research Excellence RE/18/6/34217); Rigshospitalet, University of Copenhagen (grant and non-financial support); and German Research Foundation (grants from Radiomics Priority Programme: DE 1361/19-1 [428222922] and 20-1 [428223139] in SPP2177/1) and grants from graduate program BIOQIC (GRK 2260/1 [289347353]). Open access funding provided by Semmelweis University.